Collagen, the main structural protein of the periodontium, is disorganized and destroyed during periodontal disease. The objectives of the proposed project are to study the effects of inflammation and diabetes (a common systemic disorder thought to modify periodontal disease) on gingival collagen metabolism in rats and humans. The three year project will consist of two phases. Phase I: Inflammation of the gingiva of rats will be produced by injecting endotoxin or antigen- antibody complexes into these tissues. Inflamed and non-inflamed gingiva from control and alloxan-diabetic rats will be excised, and the concentration and solubility of collagen determined prior to incubation. In other experiments, gingival fragments will be cultured on collagen gels saturated with media containing H3-proline. Collagen synthesis will be determined by measuring H3-hydroxyproline formation, and collagenolytic activity will be assessed by determining the amount of hydroxyproline solubilized from the gels as dialyzable fragments. Phase II: gingival fragments from systemically normal patients undergoing routine periodontal surgery will be studied as in phase I, after being scored for severity of inflammation (gingival index, gingival crevice fluid flow). In addition, gingival crevice fluid collagenolytic activity will be monitered in vitro; will be related to periodontal disease; and attempts will be made to determine its origin. Future experiments (phase III) will study the above parameters in diabetic humans.